The long range goal is to obtain a better understanding on a molecular level of the reaction of renin with angiotensinogen to form angiotensin I. We contend that the present lack of knowledge of the control of this reaction exists in large part because the purified components have not been available for study. It is proposed to purify and characterize normal human angiotensinogen, a high molecular weight human angiotensinogen which occurs in high estrogen states and sheep angiotensinogen. The reaction between these substances and human renin will be characterized by kinetic studies. The ability of the following substances to inhibit the reaction of human renin with normal human angiotensinogen will be documented: human alpha 1-antitrypsin, human alpha2-macroglobulin, human des-angiotensin I-angiotensinogen, and an isolated human plasma protein, designated alanine-protein, which tends to co-purify with human angiotensinogen and human plasma from certain pathological states.